Process for the manufacture of beta-alanin



separation of ?atented Jan. 16, 1945 2,367,436 PROCESS FOR THE MANUFACTURE OF fi-ALANIN Paul land, asslgnors Nutley, N. J., a corpora No Drawing. Applicat No. 456,292. In Switze 9 Claims.

p-Alanin can be obtained synthetically in various ways. One such way is the treatment of succinic acid imide with hypobromides. Lately, cyanoacetic ester was catalytically hydrogenised to p-alanin ester (Berichte der deutschen Chemischen Gesellschaft, vol. '74, year 1941, page 256). In accordance with a brief indication in "Berichte der deutschen Chemischen Gesellschaft, vol. 8, year 18'15', page 1597, c-alanin is also said to result from reduction of cyanoacetic acid with zinc and sulfuric acid. However, all these methods are not suitable for the technical production of p-alanin.

It has now been found that p-alanin can be obtained with excellent yield by a method, which can easily be carried out technically, by hydrogenising cyanoacetic acid salts in ammoniacal of a, nickel catalyst. The working can proceed in aqueous as well as in alcoholic solution. It is of advantage to use the cyanoacetic acid alkali salts. especially the potassium salt, as in this case the subsequent the alkali occurs in a very simple manner.

The advantage of the new process over the known methods for preparing p-alanin are obvious. On the one hand, cyanoacetic acid and its salts are easily accessible. As compared with the preparation from cyanoacetic ester, the principal progress is not so much to be found in the use of salts of cyanoacetic acid than in the possibility to employ nickel catalysts instead of the expensive platinum oxide, which is required when hydrogenising the ester in acid solution. Moreover, the working according to the new process can take place in alkaline solution which simplifies the question of vessels to a great extent.

The hydrogenation of cyanoacetic acid or of its salts in ammoniacal solution with a nickel catalyst proceeds very quickly when using high pressure. But it also succeeds under ordinary or slightly elevated pressure; in this case, however, it proceeds considerably more slowly. Also the temperature can vary within wide margins, the increasing of the same not causing substantially more than acceleration.

Example 1 Ruggll and Albert to Hofimann-La Roche Inc.,

tion of New Jersey Businger, Basel, Swltzer ion August 26 1942, Serial rland December 16, 1941 taken up in about 15 minutes. After filtering of! the catalyst, the filtrate is evaporated in vacuo to one-fifth of its volume, then treated with 35 parts by weight of glacial acetic acid and 100 parts by weight of water and evaporated almost to dryness. If alcohol is now added, p-alanin immediately begins to precipitate; it is absolutely pure after a single recrystallisation. The yield exceeds '75 per cent of the theoretical.

Example 2 42.6 parts by weight of cyanoacetic acid are dissolved in 50 parts by weight of water and neutralised with potassium hydroxide of 50 percent. After addition of 450 parts by weight of per cent aqueous ammonia and 20 parts by weight of a nickel catalyst, the product is hydrogenised in a shaking autoclave at 30 atmostion under alkaline conditions in the presence ofammonia and of a. nickel catalyst.

2. Process for the manufacture of betaalanine which comprises dissolving a substance selected from the group consisting of cyanoacetic acid and the salts thereof in a hydroxylated solvent selected from the group consisting of water and alcohols in the presence of a suflicient quantity of ammonia to obtain an alkaline reacting solution, and hydrogenizing said ,solution in the presence of a nickel catalyst.

3. Process for the manufacture of betaalanin'e which. comprises dissolving an alkali 20 C. After completion of the remetal salt of cyanoacetic acid in a hydroxylated solvent selected from the noun consisting of water .and alcohols, and hydrogenizing said solution under alkaline conditions in the presence of ammonia and of a nickel catalyst.

4. Process for the manufacture of betaalanine which comprises dissolving an alkali metal salt of cyanoacetic acid in a hydroxylated solvent selected from the group consisting of water and alcohols in the presence or a suflicient quantity of ammonia to obtain an alkali reacting solution, and hydrogenizins said solution in the presence of a nickel catalyst.

5. Process for the manufacture of betaalanine which comprises dissolving the potasslum salt of cyanoacetic acid in a hydroxylated solvent selected from the group consisting of water and alcohols, and hydrogenizing said solution under alkaline conditions in the presence of ammonia and of a nickel catalyst.

6. Process for the manufacture of betaalanine which comprises dissolving the potasslum salt of cyanoacetic acid in a hydroxylated accuse 

